Summary

VEGF is essential for vascular morphogenesis, with precise control of its level required for normal vascular pattern formation. Results to date have focused on the role of VEGF in many organisms, using a variety of techniques. VEGF is known to be essential for forming a vascular pattern, perhaps by recruiting angioblasts and specifying the size and location of blood vessels within the embryo. Size and location may be predetermined by a VEGF gradient, before angioblast migration. However, the mechanism of VEGF activity and the signaling pathways active during vascular morphogenesis are less clear. Further studies of VEGF action in the embryo will lead to a better understanding of VEGF activity during pathological neovascularization.

Glossary

Angioblasts: The precursor cells of endothelial cells that arise from embryonic mesoderm.

Angiogenesis: The formation of new blood vessels by sprouting from existing vessels.

EMT: The process of epithelial to mesenchymal transformation. Morphogenesis: The change in form that gives rise to the organization of cells into tissues in embryos.

Vasculogenesis: The process of vessel morphogenesis by de novo assembly of angioblasts.

References

1. Miquerol, L., Langille, B. L., and Nagy, A. (2000). Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression. Development 127, 3941-3946.

2. Damert, A., Miquerol, L., Gertsenstein, G., Risau, W., and Nagy, A. (2002). Insufficient VEGFA activity in yolk sac endoderm compro mises hematopoietic and endothelial differentiation. Development 129, 1881-1892.

3. Poole, T. J., Finkelstein, E. B., and Cox, C. M. (2001). The role of FGF and VEGF in angioblast induction and migration during vascular development. Dev. Dyn. 220, 1-17.

4. Weinstein, B. M. (2002). Plumbing the mysteries of vascular development using the zebrafish. Sem. Cell. Dev. Biol. 13, 515-522.

5. Drake, C. J., LaRue, A., Ferrara, N., and Little, C. D. (2000). VEGF regulates cell behavior during vasculogenesis. Devel. Biol. 224, 178-188.

6. Finkelstein, E. B., and Poole, T. J. (2003). Vascular endothelial growth factor: A regulator of vascular morphogenesis in the Japanese quail embryo. Anat. Rec. 272A, 403-414. A thorough analysis of the influence of ectopic VEGF on vascular morphogenesis, in which it was shown that VEGF can affect multiple processes of vasculogenesis.

7. Cleaver, O., and Krieg, P. A. (1998). VEGF mediates angioblast migration during development of the dorsal aorta in Xenopus. Development 125, 3905-3914. This paper used a variety of techniques to demonstrate the essential role of VEGF and the novel role of the Xenopus hypochord in determining dorsal aorta localization.

8. Ruhrberg, C. (2003). Growing and shaping the vascular tree: Multiple roles for VEGF. BioEssays 25, 1052-1060.

9. Gerhardt, H., Golding, M., Fruttiger, M., Ruhrberg, C., Lundkvist, A., Abramsson, A., Jeltsch, M., Mitchell, C., Alitalo, K., Shima, D., and Betsholtz, C. (2003). VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J. Cell Biol. 161, 1163-1177. This is the first demonstration that as a vascular network forms, there are two types of endothelial cells, which can sense a VEGF gradient, or proliferate, thereby determining the location and size of vessel networks.

10. Mukouyama, Y. S., Shin, D., Britsch, S., Taniguchi, M., and Anderson, D. J. (2002). Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin. Cell 109, 693-705.

Capsule Biographies

Thomas J. Poole has been studying vascular development since 1983. He has published numerous articles on the use of quail embryos and quail/chick chimeras in deciphering the origins of the embryonic vascular pattern. The current interests of his laboratory are the roles of FGF and VEGF in angioblast induction and vessel morphogenesis, and the use of arsenic in perturbation of embryonic vasculogenesis and angiogenesis.

Eric B. Finkelstein earned his Ph.D. in 2001 in Dr. Poole's laboratory, studying the role of VEGF in blood vessel morphogenesis. He is currently a postdoctoral fellow in Dr. Patricia D'Amore's laboratory in Boston, studying endothelial cell differentiation and the function of VEGF isoforms.

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